Significant alcohol and substance abuse disorders and mental health disparities have had devastating impacts in many American Indian/First Nations (Indigenous) communities. Evidence from diverse tribal groups demonstrates early onset, high frequency substance use with substantial rates of co-occurring mental disorders among Indigenous youth throughout their adolescence. Yet, how these early life patterns affect trajectories and outcomes in adulthood for Indigenous people is unknown. General population studies have shown that early adulthood (20 - 30 years of age) is a critical period of transitions in roles, responsibilities, and relationships impacting patterns of substance use and mental health. Cultural norms and contexts may translate into potentially unique developmental pathways, risks, and protective factors for Indigenous substance use and mental health outcomes. We propose to investigate these possibilities in Indigenous early adulthood, a critical period for understanding transitions from adolescence to longer-term alcohol, substance use, and mental health problems and resilience. The project will link data from our 8-wave panel study of Indigenous adolescents with 3 years of proposed new data in early adulthood. Data will be collected via computer-assisted personal interviews. The result will be the only longitudinal data set spanning Indigenous childhood, adolescent, and early adult years of which we are aware. Three major aims guide this community- based participatory research: 1) Determine trajectories of Indigenous substance use and mental health problems from late childhood to early adulthood, 2) Identify early life-course predictors of substance use and mental health among Indigenous young adults, and 3) Describe culturally appropriate definitions of wellbeing in early adulthood and document the prevalence and predictors of these positive outcomes. Results of this research will increase awareness of the nature, etiology, and consequences of alcohol, substance use, mental health problems and their comorbidity in Indigenous reservation/reserve communities. Another outcome is enhanced understanding and novel measurement of protective factors and positive Indigenous development. The results of this project have potential to inform the timing of and risk/protective factors targeted by prevention programs in Indigenous communities.